Code for Collagen Folding Deciphered

Abstract

Collagen triple helix folds in two steps: nucleation of three polypeptides at the C-termini followed by zip-chain like propagation. The triple helices found in all domains of life as well as viruses contain upto 6000 amino acids in each polypeptide that are also frequently interrupted with non-helical sequences that disrupt folding and reduce stability. Given the length of polypeptide and the disruptive interruptions, compensating mechanisms that stabilize against local unfolding during propagation and offset the entropic cost of folding the long polypeptides are not fully understood. Here, we show that the information for correct folding of collagen triple helices is encoded in their sequence as interchain electrostatic interactions. In case of humans, disrupting these interactions causes severe to lethal diseases.Key ResultCollagen triple helices found in all the three domains of life as well as viruses have converged on similar mechanism to fold correctly.

AGEing of Collagen: The Effects of Glycation on Collagen’s Stability, Mechanics and Assembly

“…The modification of lysine and arginine side-chains by AGEs will almost certainly alter salt-bridge formation within and between collagen proteins [50][51][52]. This can disrupt electrostatic interactions important in guiding the register between proteins in fibrils [48].…”